Abstract
Maintenance of skeletal muscle is essential for health and survival. There are marked losses of skeletal muscle mass as well as strength and physiological function under conditions of low mechanical load, such as space flight, as well as ground based models such as bed rest, immobilization, disuse, and various animal models. Disuse atrophy is caused by mechanical unloading of muscle and this leads to reduced muscle mass without fiber attrition. Skeletal muscle stem cells (satellite cells) and myonuclei are integrally involved in skeletal muscle responses to environmental changes that induce atrophy. Myonuclear domain size is influenced differently in fast and slow twitch muscle, but also by different models of muscle wasting, a factor that is not yet understood. Although the myonuclear domain is 3-dimensional this is rarely considered. Apoptosis as a mechanism for myonuclear loss with atrophy is controversial, whereas cell death of satellite cells has not been considered. Molecular signals such as myostatin/SMAD pathway, MAFbx, and MuRF1 E3 ligases of the ubiquitin proteasome pathway and IGF1-AKT-mTOR pathway are 3 distinctly different contributors to skeletal muscle protein adaptation to disuse. Molecular signaling pathways activated in muscle fibers by disuse are rarely considered within satellite cells themselves despite similar exposure to unloading or low mechanical load. These molecular pathways interact with each other during atrophy and also when various interventions are applied that could alleviate atrophy. Re-applying mechanical load is an obvious method to restore muscle mass, however how nutrient supplementation (e.g., amino acids) may further enhance recovery (or reduce atrophy despite unloading or ageing) is currently of great interest. Satellite cells are particularly responsive to myostatin and to growth factors. Recently, the hibernating squirrel has been identified as an innovative model to study resistance to atrophy.
Highlights
Skeletal muscle plays a significant role in quality of life and is essential for health and survival
Disuse is an expansive label for the low mechanical load or mechanical unloading of muscle; with the most severe example being that of lack of gravity in spaceflight
This study found that the earlier response was reduced stem cells (SCs) number and mitotic activity, Ferreira et al (2006) reported an intense peak of proliferating activity in SCs after 6 h of hindlimb suspension (HS) (SC duplication) followed by an increase in myonuclei at 12 h of HS (Ferreira et al, 2006)
Summary
Skeletal muscle plays a significant role in quality of life and is essential for health and survival. It is highly organized at the micro- and macroscopic level and plays a major role in mobility of the human body. Skeletal muscle accounts for ∼40% of body mass, permits precise movements and is highly adaptive. The characteristic of plasticity allows skeletal muscle to change and adapt depending on the stimuli placed upon it. Skeletal muscle has the uncanny ability to alter its phenotype depending on the mechanical load placed upon it. Physiological changes during bed rest include 6–24% reduction in muscle mass and strength (Narici and de Boer, 2011) and other disuse associated changes in skeletal muscle (Brooks et al, 2008)
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